title: Nefazodone: preclinical pharmacology of a new antidepressant.
abstract: Recent pharmacologic studies suggest that nefazodone may possess antidepressant activity. Nefazodone is active in behavioral models predictive of antidepressant potential. It is active in reversing learned helplessness, prevents reserpine-induced ptosis, and enhances response efficiency in the differential reinforcement for low rates of response paradigm. In in vitro studies, nefazodone inhibits the binding of [3H]ketanserin to cortical serotonin2 (5-HT2) binding sites, whereas in vivo, it antagonizes the 5-HT2-mediated quipazine-induced head shake in rats. In ex vivo studies, acute oral administration of nefazodone inhibits cortical serotonin uptake and occupies frontal cortical 5-HT2 receptor binding sites. Chronic administration of nefazodone produces a reduction in 5-HT2-mediated behavior and decreases cortical 5-HT2 receptor binding site density. Further, a chronic high-dose nefazodone regimen significantly potentiates 5-HT1A-mediated behavioral responses in rats. Nefazodone exhibits decreased anticholinergic, alpha-adrenolytic, and sedative activity relative to other antidepressants.
authors.affiliation: Bristol-Myers Squibb Company, Wallingford, CT 06492-7660.
authors.forename: A S
authors.initials: AS
authors.lastname: Eison
authors.forename: M S
authors.initials: MS
authors.lastname: Eison
authors.forename: J R
authors.initials: JR
authors.lastname: Torrente
authors.forename: R N
authors.initials: RN
authors.lastname: Wright
authors.forename: F D
authors.initials: FD
authors.lastname: Yocca
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D010879:Piperazines; D014230:Triazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone